tbuckley/cabot-search huggingface dataset:
Premenstrual Disorders, Timing of Menopause, and Severity of Vasomotor Symptoms
Authors: Yihui Yang, Unnur A. Valdimarsdóttir, JoAnn E. Manson, Lynnette Leidy Sievert, Bernard Leslie Harlow, A. Heather Eliassen, Elizabeth R. Bertone-Johnson, Donghao Lu
Journal: JAMA Network Open (2023)

Importance Although premenstrual disorders (PMDs) end at menopause, it is unclear whether they are associated with the timing and symptom severity of menopause. Objective To prospectively examine whether women with PMDs have increased risks of early menopause and menopause-related vasomotor symptoms (VMS). Design, Setting, and Participants This population-based cohort study was nested in the Nurses’ Health Study II (data collected from questionnaire sent between June 1991 and June 2017). Analysis of menopause timing included participants who did not have natural or surgical menopause before study entry, while the analysis of VMS was restricted to women who provided information on VMS. Data were analyzed from August 2022 to March 2023. Exposures PMDs were identified by self-reported diagnosis and confirmed with symptom questionnaires from 1991 to 2005. Participants were age-matched to women without PMD diagnoses and confirmed absence of or minimal premenstrual symptoms. Main Outcomes and Measures During follow-up through 2017, timing of natural menopause was assessed biennially, and VMS were assessed in 2009, 2013, and 2017. The association of PMDs with early menopause was assessed by Cox proportional hazards models and with VMS by logistic regression models. Results Of 1220 included women with PMDs, the median (IQR) age was 40.7 (37.3-43.8) years; of 2415 included women without PMDs, the median (IQR) age was 41.7 (38.3-44.8) years. The median (IQR) follow-up in this study was 20.3 (17.8-22-2) years. Early natural menopause (menopause before age 45 years) was reported by 17 women with PMDs (7.1 per 1000 person-years) and 12 women without PMDs (2.7 per 1000 person-years; adjusted hazard ratio, 2.67; 95% CI, 1.27-5.59). In addition, 795 women with PMDs (68.3%) and 1313 women without PMDs (55.3%) reported moderate or severe VMS (adjusted odds ratio, 1.68; 95% CI, 1.32-2.14). There was no observed association between PMDs and mild VMS (adjusted odds ratio, 0.99; 95% CI, 0.76-1.28). Conclusions and Relevance In this cohort study of US women, PMDs were associated with increased risks of early menopause and moderate or severe VMS. PMDs may be indicative of underlying physiology linked to early menopause and VMS, suggesting a phenotype observable during the reproductive years that may allow clinicians to target women at risk of earlier menopause and subsequent health risks later in the life course.
Skilled Nursing Facility Changes in Ownership and Short-Stay Medicare Patient Outcomes
Authors: Rachel A. Prusynski, Andrew Humbert, Tracy M. Mroz
Journal: JAMA Network Open (2023)

Skilled nursing facility (SNF) changes in ownership are receiving attention in the national conversation regarding health care quality and oversight. SNF ownership changes have been cited as possible ways for SNFs to obscure financial arrangements and shift funds away from patient care; however, it is unclear whether ownership changes are associated with quality outcomes, especially for short-stay patients.To determine which SNF characteristics are associated with changes in ownership and whether ownership changes were associated with differences in short-stay patient outcomes.This cohort study was a secondary analysis of 2016 to 2019 Medicare administrative data including SNFs in the United States with complete data. Data were analyzed from January 2016 through December 2019.SNF change in ownership.Outcomes of interest were facility-level risk-adjusted rates of hospital readmissions, emergency department visits, and community discharge for short-stay patients after admission to an SNF. Analyses were conducted using multivariable logistic regression and controlled interrupted time series.Of 11 004 SNFs, 1459 (13.26%) changed ownership between 2016 and 2019. Compared with for-profit SNFs, nonprofit and government SNFs had lower odds of changing ownership (nonprofit: odds ratio [OR], 0.40; 95% CI, 0.32-0.49; government: OR, 0.26; 95% CI, 0.17-0.41). Chain SNFs had higher odds of changing ownership than nonchain SNFs (OR, 1.38; 95% CI, 1.21-1.59). Urban SNFs with lower occupancy rates (OR per 10-percentage-point decrease, 1.19; 95% CI, 1.14-1.25), larger Medicaid populations (OR per 10-percentage-point increase, 1.17; 95% CI, 1.13-1.22), and lower staffing ratings (OR per 1-star increase on staffing rating, 1.18; 95% CI, 1.14-1.25) had higher odds of changing ownership. Descriptively, all 3 quality outcomes were worse throughout the study in SNFs undergoing ownership change compared with controls that did not change ownership. However, results of interrupted time series models found no associations between an ownership change and hospital readmissions or community discharge rates. Ownership change was associated with a short-term increase of 0.32 (95% CI, 0.03 to 0.62) percentage points in emergency department visits.In this cohort study of 11 004 SNFs in the US between 2016 and 2019, SNF characteristics historically associated with lower quality were more likely to change ownership; however, ownership changes were only associated with short-term increases in ED visits. These results suggest that SNF ownership changes may be a symptom, not a cause, of lower quality.
Screening for Hypertensive Disorders of Pregnancy in the US—A New Hypertensive Urgency
Authors: Srilakshmi Mitta, Cary P. Gross, Melissa A. Simon
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Correlative CD4 and CD8 T-cell immunodominance in humans and mice: Implications for preclinical testing
Authors: Tertuliano Alves Pereira Neto, John Sidney, Alba Grifoni, Alessandro Sette
Journal: Cellular and Molecular Immunology (2023)

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex (MHC) molecules, and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood. In this study, we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase (IEDB) database. We first analyzed SARS-CoV-2 spike (S) and nucleoprotein (N), which are two common targets of the immune response and well studied in both human and mouse systems. We observed a weak but statistically significant correlation between human and H-2
Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial
Authors: Jiang Ji, Ziqi Wan, Jing Ruan, Yuan Yang, Qinglin Hu, Zesong Chen, Chen Yang, Miao Chen, Bing Han
Journal: Blood Cancer Journal (2023)

This trial compared eltrombopag (EPAG)+tacrolimus and EPAG monotherapy in patients with refractory/relapsed acquired aplastic anaemia (AA). Patients with refractory/relapsed AA were randomly assigned to receive either EPAG+tacrolimus or EPAG monotherapy at a ratio of 2:1. Patient response, safety, clonal evolution and survival were compared. In total, 114 patients were included in the analysis, with 76 patients receiving EPAG+tacrolimus and 38 receiving EPAG only. With a median follow-up of 18 (6-24) months, the overall response rate (ORR) for patients treated with EPAG+tacrolimus and EPAG alone was 38.2% vs. 31.6% (P = 0.490) at the 3rd month, 61.8% vs. 39.5% (P = 0.024) at the 6th month, 64.5% vs. 47.1% (P = 0.097) at the 12th month, and 60.5% vs. 34.2% (P = 0.008) at the last follow-up. The rate of each adverse event, overall survival curves (P = 0.635) and clonal evolution rate (P = 1.000) were comparable between the groups. A post hoc subgroup analysis showed that EPAG+tacrolimus could have advantage over EPAG monotherapy in terms of the ORR at the 6th month (P = 0.030)/last follow-up (P = 0.013) and the cumulative relapse-free survival (RFS) curves (P = 0.048) in patients <60 years old.
Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome
Authors: Jing Sun, Jianhui Zhao, Fangyuan Jiang, Lijuan Wang, Qian Xiao, Fengyan Han, Jie Chen, Shuai Yuan, Jingsun Wei, Susanna C. Larsson, Honghe Zhang, Malcolm G Dunlop, Susan M Farrington, Kefeng Ding, Evropi Theodoratou, Xue Li
Journal: Genome Medicine (2023)

Abstract Background The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods Protein quantitative trait loci (pQTLs) were derived from seven published genome-wide association studies (GWASs) on plasma proteome, and summary-level data were extracted for 4853 circulating protein markers. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4957 cases and 304,197 controls), and the UK Biobank (9276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which four (GREM1, CLSTN3, CSF2RA, CD86) were prioritized with the most convincing evidence. These protein-coding genes are mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusions This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.
Effect of invitation letter in language of origin on screening attendance: randomised controlled trial in BreastScreen Norway
Authors: Solveig Hofvind, Nadia Iqbal, Jonas E Thy, Gunhild Mangerud, Sameer Bhargava, Sophia Zackrisson, Paula Berstad
Journal: BMJ (2023)

Abstract Objective To explore attendance at organised mammographic screening among immigrant groups that received an invitation letter and information leaflet (invitation) in their language of origin and Norwegian compared with Norwegian only. Design Randomised controlled trial. Setting Population based screening programme for breast cancer in Norway (BreastScreen Norway), which invites women aged 50-69 to two-view mammographic screening biennially. Participants All women invited to BreastScreen Norway in the study period April 2021 to June 2022 whose language of origin was Arabic (women born in Algeria, Egypt, Lebanon, Iraq, Palestine, Sudan, Syria, Tunisia, or Morocco), English (women born in the Philippines), Polish (women born in Poland), Somali (women born in Somalia), or Urdu (women born in Pakistan) (n=11 347). Intervention The study group received an invitation to screening in their language of origin and in Norwegian, whereas the control group received an invitation in Norwegian only during the study period. Main outcome measure Attendance at BreastScreen Norway during the study period. Results Overall attendance was 46.5% (2642/5683) in the study group and 47.4% (2682/5664) in the control group. No statistical differences in attendance were observed after stratification by language of invitation, age at invitation, or years since immigration. Conclusions No difference in attendance was observed between immigrant women invited to BreastScreen Norway in their language of origin and in Norwegian compared with Norwegian only. Several barriers to cancer screening may exist among immigrants, and translating the invitation is probably only a part of a complex explanation. Trial registration NCT04672265.ClinicalTrials.gov NCT04672265 .
Unethical pharmaceutical marketing: a common problem requiring collective responsibility
Authors: Shai Mulinari, Piotr Ozieranski
Journal: BMJ (2023)

Shai Mulinari and Piotr Ozieranski argue healthcare professionals and organisations should respond more forcefully to unethical marketing and support stronger regulatory action The marketing practices used by pharmaceutical companies have been a longstanding concern,12 with controversial techniques including the use of medical opinion leaders and third parties such as patient advocacy groups. In many jurisdictions, including Europe,3 Japan,4 Canada,5 and Australia,6 marketing by pharmaceutical companies is largely regulated by the industry itself, based on codes of practice drawn up by national industry trade groups. The UK has one of the most advanced and extensively studied self-regulatory systems in Europe78910 and globally (box 1).34 Box 1 ### UK's pharmaceutical industry self-regulation Oversight of prescription drug marketing in the UK is delegated by the medicines and medical device regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), to the industry trade group, the Association of the British Pharmaceutical Industry (ABPI), and its self-regulatory body, the Prescription Medicines Code of Practice Authority (PMCPA).7 The PMCPA's jurisdiction is accepted by virtually all drug companies operating in the UK, including about 70 ABPI members and over 60 non-members that follow the ABPI code voluntarily.11 #### PMCPA sanctions Companies found to be in breach of the ABPI code are required to pay "administrative charges" to contribute to the costs of processing complaints.11 These charges, which are explicitly defined as not being fines, are typically £3500 but increase to £12 000 if an appeal against a ruling is unsuccessful. In cases of more serious wrongdoing, the PMCPA can publicly reprimand a company or require it to issue a corrective statement. For both sanctions the company pays the cost of advertising these in medical ( The BMJ ), pharmaceutical ( Pharmaceutical Journal ), and nursing ( Nursing Standard ) publications. The PMCPA can also request compulsory audit of a … RETURN TO TEXT
Association between subclinical atherosclerosis and cardiac structure and function—results from the UK Biobank Study
Authors: Judit Simon, Kenneth Fung, Zahra Raisi-Estabragh, Nay Aung, Mohammed Y Khanji, Emese Zsarnóczay, Béla Merkely, Patricia B Munroe, Nicholas C Harvey, Stefan K Piechnik, Stefan Neubauer, Paul Leeson, Steffen E Petersen, Pál Maurovich-Horvat
Journal:  (2023)

Abstract Aims Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease. Methods and results Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals (61.6 ± 7.5 years, 45.9% male) were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all P &amp;lt; 0.05). Conclusion Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.
Corrigendum to “EASL clinical practice guidelines on sclerosing cholangitis” [J Hepatol (77) 761–806]
Authors: Olivier Chazouilleres, Ulrich Beuers, Annika Bergquist, Tom Hemming Karlsen, Cynthia Levy, Marianne Samyn, Christoph Schramm, Michael Trauner
Journal: Journal of Hepatology (2023)
PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B
Authors: Ho Soo Chun, George V. Papatheodoridis, Minjong Lee, Hye Ah Lee, Yeong Hwa Kim, Seo Hyun Kim, Yun-Seo Oh, Su Jin Park, Jihye Kim, Han Ah Lee, Hwi Young Kim, Tae Hun Kim, Eileen L. Yoon, Dae Won Jun, Sang Hoon Ahn, Vana Sypsa, Cihan Yurdaydin, Pietro Lampertico, Jose Luis Calleja, Harry LA. Janssen, George N. Dalekos, John Goulis, Thomas Berg, Maria Buti, Seung Up Kim, Yoon Jun Kim
Journal: Journal of Hepatology (2023)
Definitive radiation therapy for inoperable stage III/IV cutaneous squamous cell carcinoma: A single-institution retrospective cohort study
Authors: Emily E. Granger, Emily Y. Kim, Emily E. Karn, Morgan K. Groover, Ann W. Silk, Danielle N. Margalit, Roy B. Tishler, Jonathan D. Schoenfeld, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2023)
Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy
Authors: Youngjoo Lee, Sukyung Song, Suah Yang, Jinseong Kim, Yujeong Moon, Nayeon Shim, Hong Yeol Yoon, Sehoon Kim, Man Kyu Shim, Kwangmeyung Kim
Journal: Acta Pharmaceutica Sinica B (2023)

Immune checkpoint blockade (ICB) therapy targeting PD-L1 via monoclonal antibody (mAb) has shown extensive clinical benefits in the diverse types of advanced malignancies. However, most patients are completely refractory to ICB therapy owing to the PD-L1 recycling mechanism. Herein, we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes (immune checkpoint blockade liposomes; ICB-LPs) to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor cells. The ICB-LPs are prepared by formulation of DC8,9PC with photo-polymerized diacetylenic moiety, 1,2-dipalmitoylphosphatidylcholine (DPPC) and anti-PD-L1 peptide (D-form NYSKPTDRQYHF)-conjugated DSPE-PEG2k (anti-PD-L1-DSPE-PEG2k) in a molar ratio of 45:45:10, followed by cross-linking of liposomal bilayer upon UV irradiation. The 10 mol% anti-PD-L1-DSPE-PEG2k incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7 ± 1.04 nm, showing a high stability in serum condition. Importantly, the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane, which are endocytosed with aim to deliver PD-L1 to the lysosomes, wherein the durable PD-L1 degradation is observed for 72 h, in contrast to anti PD-L1 mAbs showing the rapid PD-L1 recycling within 9 h. The in vitro co-culture experiments with CD8+ T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 axis. When ICB-LPs are intravenously injected into colon tumor-bearing mice, they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting, inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 degradation. Collectively, this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward the lysosomes instead of the recycling endosomes.
A generalized driving risk assessment on high-speed highways using field theory
Authors: Yang-Jun Joo, Eui-Jin Kim, Dong-Kyu Kim, Peter Y. Park
Journal: Analytic Methods in Accident Research (2023)

This study presents a new safety measure derived from field theory. It evaluates the risk arising from the various concurrent conflicts within a platoon that can occur on high-speed highway driving situations, such as car-following, yielding, and lane changing. We defined the risk field as a finite scalar field produced by traveling vehicles on the road, and we defined the conflict field as the overlapping risk field between any vehicles in proximity on the roadway. The study used a probabilistic trajectory prediction model to construct risk fields and an approximation method to reduce the computational time for real-time applications. To demonstrate the applicability of the proposed new measure, we applied it to real-world trajectory data (NGSIM data from US Highway 101). We compared the results with three traditional conflict-based safety measures: post-encroachment time (PET), modified time-to-collision (MTTC), and deceleration rate to avoid a crash (DRAC). The new measure produced seamless and continuous risk estimations even during time windows when the other measures could not estimate the risk between vehicles. This is a major advantage over traditional measures. The study also developed visual displays of the estimated conflict fields to provide safety analysts with an intuitive and fast understanding of the results of the safety assessments made using the conflict field measure. We conclude that the proposed new safety measure provides a robust, reliable, and improved assessment of the risk involved in expected future mixed-traffic environments that involve both human-driven vehicles and automated vehicles in the future.